The long-term goal of this research is to develop a unified structure of biological concepts relating to certain bacteria, principally members of Neisseria and Haemophilus, which inhabit a unique and restricted ecological niche--the mucous membranes of human beings. A large amount of genetic variation has been recognized recently in strains of N. gonorrhoeae isolated from patients. The differences affect various biosynthetic pathways as well as the more conspicuous resistances to antibacterial drugs. We are characterizing more than one thousand strains of N. gonorrhoeae and other species of Neisseria cultured from patients or normal persons. Representatives of the mutant gene loci of these bacteria will be examined in transformation experiments designed to develop a genetic map of their drug resistance and auxotrophic genes. These organisms are evolving as a result of diverse selective influences operating in their natural habitat. This investigation will elucidate various features of the phenotypic and genetic changes, and attempt to determine their possible relations to virulence and to persistence in the tissues of some patients in spite of treatment with antibiotics. Because of the paucity of bacteriological tests used to differentiate members of the Neisseriaceae, much of the taxonomy of these bacteria is based on trivial or unreliable features. Therefore, I plan to examine some taxonomic relations among the various members of this family using genetic as well as orthodox bacteriological methods.